Because aged nonhuman primates show ?-amyloid (A?) deposition in senile plaques and blood vessels similar to that seen in human aging and AD, C-terminal-specific antibodies to A?40 and A?42 were used to investigate A? peptide length in the brains of 11 aged rhesus monkeys and a 59-year-old chimpanzee. In contrast to AD, where the earliest and most prominent form of A? in senile plaques is A?42 in the monkey, A?40-positive plaques predominated. The ratio of A?40:A?42-positive plaques averaged 2.08 in the monkey, as compared to a mean ratio of 0.37 in 68 human AD subjects (p < 0.001). A?40 was also more prominent in the chimpanzee than in humans. Possible explanations for these findings include species differences in the cleavage of A? from the amyloid precursor protein or in the activity of a putative carboxy peptidase forming A?40 from A?42 in situ.